用于光动力疗法（PDT）的天然和人工酶制氧系统是为肿瘤治疗而开发的，但它们尚未达到预期的疗效。此外，酶和光敏剂通常都需要载体才能有效递送至肿瘤部位。在这里，通过巧妙地将自级联增强的 PDT 与 Zn2 超载疗法结合起来，开发了一种自级联增强的多模式肿瘤治疗。锰卟啉 (TCPP-Mn) 被选为光敏剂和过氧化氢酶 (CAT) 模拟物，可封装在葡萄糖氧化酶 (GOx) 内。采用酸响应型咪唑骨架分子筛8（ZIF-8）作为TCPP-Mn@GOx（T@G）的载体，得到TCPP-Mn@GOx@ZIF-8（T@G@Z）。 T@G@Z表现出强大的抗肿瘤能力：ZIF-8结构降解后，GOx可以介导葡萄糖氧化并产生过氧化氢（H2O2）； TCPP-Mn可以催化H2O2转化为O2，用于自级联增强PDT；同时，释放的Zn2可通过破坏线粒体膜电位，增强氧化应激，诱发线粒体功能障碍；此外，还可以启动免疫治疗来抵抗原发肿瘤和肿瘤转移。自级联增强的 T@G@Z 展示了其在进一步肿瘤管理方面的潜在应用。© 2024 Wiley‐VCH GmbH。

Natural and artificial enzyme oxygen-generating systems for photodynamic therapy (PDT) are developed for tumor treatment, yet they have fallen short of the desired efficacy. Moreover, both the enzymes and photosensitizers usually need carriers for efficient delivery to tumor sites. Here, a self-cascade-enhanced multimodal tumor therapy is developed by ingeniously integrating self-cascade-enhanced PDT with Zn2+-overloading therapy. Manganese-porphyrin (TCPP-Mn) is chosen both as the photosensitizer and catalase (CAT) mimic, which can be encapsulated within glucose oxidase (GOx). Acid-responsive zeolitic imidazolate framework-8 (ZIF-8) is applied as the carrier for TCPP-Mn@GOx (T@G), attaining TCPP-Mn@GOx@ZIF-8 (T@G@Z). T@G@Z demonstrates robust anti-tumor ability as follows: upon the structural degradation of ZIF-8, GOx can mediate the oxidation of glucose and generate hydrogen peroxide (H2O2); TCPP-Mn can catalyze H2O2 into O2 for self-cascade-enhanced PDT; meanwhile, the released Zn2+ can enhance oxidative stress and induce mitochondrial dysfunction by destroying mitochondrial membrane potential; furthermore, immunotherapy can be activated to resist primary tumor and tumor metastasis. The self-cascade-enhanced T@G@Z exhibited its potential application for further tumor management.© 2024 Wiley‐VCH GmbH.